When he was 15, Sidney O.'s hair began turning gray. His parents thought this was strange, but because Sidney had no history of health problems, they dismissed this anomaly as nothing serious.

Within five years, however, Sidney was almost completely bald with a sparse, gray beard and nearly no pubic hair. By age 30, he looked like an old man. The boy also had developed hyperkeratosis--the abnormal growth of skin corns--on both feet. His skin began to wrinkle and cataracts formed in both eyes. Osteoporosis, arthritis and arteriosclerosis struck eight years later. Old before his time, Sidney O. is a victim of Werner's Syndrome, a rare inherited disease that causes an accelerated physical decline similar to aging. Victims of this disease suffer from heart disease, cancer and a host of other maladies that usually do not occur until later in life. The fate of Sidney O.--an anonymous case study in the medical books--is unknown to us, but most Werner's patients die before age 50. And some die much sooner.

Werner's Syndrome has long been a fascinating puzzle for aging experts, who wondered whether an understanding of the disease could lead to an understanding of the natural aging process. But scientists have never had a clue to the cause of this condition--until now.

After examining Werner's Syndrome victims in Japan and Syria, a team of scientists led by Gerard Schellenberg, a geneticist at the Veterans Affairs Puget Sound Health Care System in Seattle, believe they have found the gene responsible for the disease. "The exciting thing is that this is the first human gene discovered that's associated with aging," Schellenberg said. "This is the biggest step taken so far in finding out what may be happening to us on a molecular level when we age." The helicase enzyme unwinds the strands of DNA to prepare the molecule for activies such as replication and repair. The Werner's gene appears to be responsible for manufacturing a type of protein known as a helicase--an enzyme that unwinds DNA molecules, according to Schellenberg. DNA unwinding is necessary for cell replication and repair, and Schellenberg believes that a mutated Werner's gene may cause errors to occur during these molecular activities. "We've long thought that DNA damage is at least one component of the aging process," Schellenberg said.

In their report in the April 12 edition of the journal Science, Schellenberg and his team said the discovery raises the question of whether different versions of the gene affect the life spans of people without the disease, and if there exist variations of the gene that protect against aging. "The interesting part will be discovering exactly how this gene participates in the aging of an average, ordinary person," said George Martin, a pathologist at the University of Washington in Seattle and a co-author of the report. According to Martin, Werner's Syndrome is an extremely rare disease with only 500 known cases in the U.S. The disease is inherited only when the offspring receives a mutant version of the gene from both parents. The syndrome is named after Carl Wilhem Otto Werner, a German physician who in 1904 wrote a thesis about a family afflicted with what appeared to be premature aging.

Almost ten years ago, Martin set up a database that attempted to register all known Werner's Syndrome patients throughout the world. When Schellenberg and his team began looking for the Werner's gene in 1992, that database provided a starting point for the hunt. Japan and Syria provided a prominent number of Werner's victims due to the high frequency of intermarriages in the two countries. The Werner's gene was found to have a genetic sequence that closely resembles the sequence of genes that code for helicases, so Schellenberg assumes that this gene also codes for one, though this has not been proven directly. If the gene does code for a DNA-unwinding helicase, this indicates that DNA transactions are an important part of the onset of the disease, Schellenberg said. Dr. David Smith discusses how it is an over-simplification to call this discovery the "aging" gene.

But important differences exist between the afflictions of Werner's Syndrome and natural aging. "Werner's patients don't get Alzheimer's disease or high blood pressure," said David E. Smith, a professor at Northwestern University's Department of Pathology and the Buehler Center on Aging. "They also only suffer from a limited range of all possible cancers. There are several components of real aging that are simply missing here."

David Finkelstein agrees. A geneticist at the National Institute on Aging, Finkelstein said the newly discovered gene might better be described as a cancer agent instead of an aging gene. "One thing that happens with age is that incidents of cancer go up," Finkelstein said. "There's an awful lot of different kinds of cancer out there. It could be that this gene is responsible for specific types of cancer where some of the effects appear as premature aging." Also, discovering the Werner's gene is a long way from discovering a cure, Finkelstein said. In a Werner's Syndrome victim, every cell contains the mutant gene and there's no known way to combat its effects. Still, Finkelstein believes that the discovery is the biggest step taken in aging research in years.

For now, scientists will be busy determining just how well Werner's Syndrome mimics the molecular decay that happens during natural aging, Finkelstein said. "Aging research is in the dark age," Finkelstein said. "It's remarkable how little we know. Now we know a little more, but just a little."